Chronic Diseases and Translational Medicine最新文献

Background

The global prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The pathogenesis of NAFLD is multifaceted, and the underlying mechanisms are elusive. We conducted data mining analysis to gain a better insight into the disease and to identify the hub genes associated with the progression of NAFLD.

Methods

The dataset GSE49541, containing the profile of 40 samples representing mild stages of NAFLD and 32 samples representing advanced stages of NAFLD, was acquired from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the R programming language. The Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database were used to perform the enrichment analysis and construct protein–protein interaction (PPI) networks, respectively. Subsequently, transcription factor networks and key modules were identified. The hub genes were validated in a mice model of high fat diet (HFD)-induced NAFLD and in cultured HepG2 cells by real-time quantitative PCR.

Results

Based on the GSE49541 dataset, 57 DEGs were selected and enriched in chemokine activity and cellular component, including the extracellular region. Twelve transcription factors associated with DEGs were indicated from PPI analysis. Upregulated expression of five hub genes (SOX9, CCL20, CXCL1, CD24, and CHST4), which were identified from the dataset, was also observed in the livers of HFD-induced NAFLD mice and in HepG2 cells exposed to palmitic acid or advanced glycation end products.

Conclusion

The hub genes SOX9, CCL20, CXCL1, CD24, and CHST4 are involved in the aggravation of NAFLD. Our results offer new insights into the underlying mechanism of NAFLD progression.

Treatment of multiple myeloma (MM) has advanced dramatically in the past two decades. However, under the conditions of the COVID-19 pandemic, treatment strategies have been modified accordingly. Numerous novel agents, updated trials, and major advances in myeloma have been reported in the American Society of Hematology 2020 annual meeting, either for transplant-eligible or ineligible patients. Hot topics such as the significance of autologous stem cell transplantation (ASCT), development of novel agents, and chimeric antigen receptor-T (CAR-T) cells have been widely discussed. The triplet regimen bortezomib, lenalidomide, and dexamethasone (VRd) is recommended as the standard first-line treatment, and the addition of a fourth drug improves efficacy and survival. The value of ASCT remains undoubtful, even in the era of quadruplet induction. Dual-drug maintenance, including proteasome inhibitors and immunomodulatory drugs, overcomes unfavorable outcomes in high-risk patients. For relapsed/refractory myeloma (RRMM) patients, novel agents such as selinexor and venetoclax are superior. CAR-T cells and other cell-surface-targeted therapies also appear promising.

Vascular access is the lifeline of hemodialysis patients. There are great differences in the establishment and use of vascular access in different countries and regions around the world. We believe that on the basis of good evaluation and planning, it is recommended that hemodialysis patients choose native arteriovenous fistula first. In view of the new progress of vascular access views domestic and international at home and abroad in recent years, we organized experts to recommend the establishment and maintenance of arteriovenous fistula (AVF) for the Chinese population, including preoperative evaluation and planning of the establishment of AVF, AVF surgery, perioperative drug intervention measures and postoperative maintenance, and put forward suggestions for future research directions. The recommendations in this consensus are general and clinicians need to make treatment decisions based on the actual situation.

Background

Leukocyte telomere length shortening is a characteristic of premature senescence, a process that can be accelerated by oxidative stress. In general, patients with end-stage renal disease undergoing regular hemodialysis (HD) are repeatedly exposed to oxidative stress. Patients undergoing HD tend to have cardiovascular diseases associated with oxidative stress and inflammation. Therefore, we assumed that telomere length is associated with HD vintage and the degree of vascular calcification.

Methods

A total of 144 patients undergoing regular HD before kidney transplantation and 62 patients on hemodialysis, but not undergoing kidney transplantation, were enrolled. We measured common laboratory values, such as calcium, phosphate, and hemoglobin levels, and assessed the degree of vascular calcification in the patients. The leukocyte telomere length was measured using reverse transcription polymerase chain reaction, and Spearman correlation was used for correlation analysis.

Results

The leukocyte telomere length was negatively associated with age (rho = −0.306, P＜0.01); it was shorter in middle-aged patients than in young patients (13.48 ± 4.80 vs. 15.86 ± 4.51, P < 0.01). The telomere length was significantly different among patients aged 52–74 years in groups with different HD vintages. Additionally, the telomere length was positively associated with serum hemoglobin (Hb) levels in all patients (rho = 0.290, P < 0.01). There was a significant difference among patients divided into three groups according to the degree of anemia (17.09 ± 5.64 vs. 14.40 ± 4.07 vs. 13.99 ± 3.95, P < 0.01). Further, a significant difference was observed in the telomere length among patients with different degrees of vascular calcification (16.79 ± 4.91 vs. 13.61 ± 2.82 vs. 14.62 ± 3.63 vs. 10.71 ± 3.74, P < 0.01). The telomere length was shorter in the patients on hemodialysis who did not receive a kidney transplant than in the surgical patients (8.12 ± 1.83 vs. 14.33 ± 4.63, P < 0.01).

Conclusion

This study demonstrated that the telomere length was significantly correlated with HD vintage in patients of a certain age group. The telomere length was shorter in patients on hemodialysis who matched for age and dialysis vintage with kidney transplant patients. It was also associated with vascular calcification and serum Hb levels in all patients undergoing HD.

Background

High sodium intake is an important risk factor for hypertension and cardiovascular disease. However, the association between gut microbiota composition and metabolomic profiles with dietary sodium intake and blood pressure (BP) is not well-understood. The metabolome, microbiome, and dietary salt intervention (MetaSalt) study aimed to investigate microbial and metabolomic profiles related to dietary sodium intake and BP regulation.

Methods

This family-based intervention study was conducted in four communities across three provinces in rural northern China in 2019. Probands with untreated prehypertension or stage-1 hypertension were identified through community-based BP screening, and family members including siblings, offspring, spouses, and parents were subsequently included. All participants participated in a 3-day baseline examination with usual diet consumption, followed by a 10-day low-salt diet (3 g/d of salt or 51.3 mmol/d of sodium) and a 10-day high-salt diet (18 g/d of salt or 307.8 mmol/d of sodium). Differences in mean BP levels were compared according to the intervention phases using a paired Student's t-test.

Results

A total of 528 participants were included in this study, with a mean age of 48.1 years, 36.7% of whom were male, 76.8% had a middle school (69.7%) or higher (7.1%) diploma, 23.4% had a history of smoking, and 24.4% were current drinkers. The mean arterial pressure at baseline was 97.2 ± 10.5 mm Hg for all participants, and significantly decreased during the low-salt intervention (93.8 ± 9.3, P < 0.0001) and subsequently increased during the high-salt intervention (96.4 ± 10.0, P < 0.0001).

Conclusions

Our dietary salt intervention study has successfully recruited participants and will facilitate to evaluate the effects of gut microbiota and metabolites on BP regulation in response to sodium burden, which will provide important evidence for investigating the underlying mechanisms in the development of hypertension and subsequent cardiovascular diseases.

Trial registration

The study was registered in the Chinese Clinical Trial Registry database (ChiCTR1900025171).